lung cancer. What is cancer of the lung?. Disruption of the system of checks and balances on cell growth results in an uncontrolled division and proliferation of cells that eventually forms a mass known as a tumor. .
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Since lung cancer tends to spread, or metastasize, very early in its course, it is a very life-threatening cancer and one of the most difficult cancers to treat. While lung cancer can spread to any organ in the body, certain organs – particularly the adrenal glands, liver, brain, and bone - are the most common sites for lung cancer metastasis.
Lung cancers can arise in any part of the lung. Ninety to 95% of cancers of the lung are thought to arise from the epithelial, or lining cells of the larger and smaller airways (bronchi and bronchioles); for this reason lung cancers are sometimes called bronchogenic carcinomas. Cancers can also arise from the pleura (the thin layer of tissue that surrounds the lungs), called mesotheliomas, or rarely from supporting tissues within the lungs, for example, blood vessels.
Lung cancer was not common prior to the 1930s but increased dramatically over the following decades as tobacco smoking increased. In many developing countries, the incidence of lung cancer is beginning to fall following public education about the dangers of cigarette smoking and effective smoking cessation programs. Nevertheless, lung cancer remains the most common form of cancer in men worldwide and the fifth most common form of cancer in women.
What causes lung cancer?SmokingThe incidence of lung cancer is strongly correlated with cigarette smoking, with about 90% of lung cancers arising as a result of tobacco use. The risk of lung cancer increases with the number of cigarettes smoked over time; doctors refer to this risk in terms of pack-years of smoking history (the number of packs of cigarettes smoked per day multiplied by the number of years smoke. While the risk of lung cancer is increased with even a 10 pack-year smoking history, those with 30 pack-year histories or more are considered to have the greatest risk for the development of lung cancer. Among those who smoke two or more packs of cigarettes per day, one in seven will die of lung cancer.
Pipe and cigar smoking can also cause lung cancer, although the risk is not as high as with cigarette smoking. While someone who smokes one pack of cigarettes per day has a risk for the development of lung cancer that is 25 times higher than a nonsmoker, pipe and cigar smokers have a risk of lung cancer that is about five times that of a nonsmoker.
Tobacco smoke contains over 4,000 chemical compounds, many of which have been shown to be cancer-causing, or carcinogenic. The two primary carcinogens in tobacco smoke are chemicals known as nitrosamines and polycyclic aromatic hydrocarbons. The risk of developing lung cancer decreases each year following smoking cessation as normal cells grow and replace damaged cells in the lung. In former smokers, the risk of developing lung cancer begins to approach that of a nonsmoker about 15 years after cessation of smoking.
Passive smokingPassive smoking, or the inhalation of tobacco smoke from other smokers sharing living or working quarters, is also an established risk factor for the development of lung cancer. Research has shown that non-smokers who reside with a smoker have a 24% increase in risk for developing lung cancer when compared with other non-smokers. An estimated 3,000 lung cancer deaths occur each year in the U.S. that are attributable to passive smoking.
No symptoms - In up to 25% of people who get lung cancer, the cancer is first discovered on a routinechest x-ray or CT scan as a solitarysmall mass sometimes called a coinlesion. These patients with small single masses often report no symptoms of lung cancer at the time it is discovered.
Symptoms related to the cancer – The growth of the cancer and invasion of lung tissues and surroundings may interfere with breathing, leading to symptoms such as cough, shortness of breath, wheezing, chest pain, and coughing up blood (hemoptysis). If the cancer has invaded nerves, for example, it may cause shoulder pain that travels down the outside of the arm (called Pancoast’s Syndrome)
or paralysis of the vocal cords leading tohoarseness. Invasion of the esophagus may lead to difficulty swallowing (dysphagia). If a large airway is obstructed, collapse of a portion of the lung may occur and cause infections (abscesses, pneumonia) in the obstructed area.
Symptoms related to metastasis – Lung cancer that has spread to the bones may produce excruciating pain at the sites of bone involvement. Cancer that has spread to the brain may cause a number of neurologic symptoms that may include blurred vision, headaches, seizures, or symptoms of stroke such as weakness or loss of sensation in parts of the body.
Paraneoplastic symptoms - Lung cancers frequently are accompanied by so-called paraneoplastic syndromes that result from production of hormone-like substances by the tumor cells. Paraneoplastic syndromes occur most commonly with SCLC but may be seen with any tumor type.
A common paraneoplastic syndrome associated with SCLC is the production of a hormone called adrenocorticotrophic hormone (ACTH) by the cancer cells, leading to oversecretion of the hormone cortisol by the adrenal glands (Cushing’s Syndrome). The most frequent paraneoplastic syndrome seen with NSCLC is the production of a substance similar to parathyroid hormone, resulting in elevated levels of calcium in the bloodstream.
The chest x-ray is the most common first diagnostic step when any new symptoms of lung cancer are present. Chest x-rays may reveal suspicious areas in the lungs but are unable to determine if these areas are cancerous. In particular, calcified nodules in the lungs or benign tumors called hamartomas may be identified on a chest x-ray and simulate lung cancer.
CT (computerized axial tomography scan, or CAT scan) scans may be performed on the chest, abdomen, and/or brain to examine for both metastatic and primary tumor. A CT scan of the chest may be ordered when x-rays are negative or do not yield sufficient information about the extent or location of a tumor
Sometimes intravenous contrast material is given prior to the procedure to help delineate the organs and their positions
A CT scan exposes the patient to a minimal amount of radiation.
helical CT scan (or spiral CT scan) is sometimes used in screening for lung cancers. This procedure requires a special type of CAT scanner. The heightened sensitivity of this method is actually one of the sources of its drawbacks, since lung nodules requiring further evaluation will be seen in approximately 20% of people with this technique. Ninety percent of the nodules identified by low-dose helical screening CTs are not cancerous, but require up to two years of costly and often uncomfortable follow-up and testing.
(MRI) scans may be indicated when precise detail about a tumor’s location is required.. There are no known side effects of MRI scanning, and there is no exposure to radiation. The image and resolution produced by MRI is quite detailed and can detect tiny changes of structures within the body. People with heart pacemakers, metal implants, artificial heart valves, and other surgically implanted structures cannot be scanned with an MRI because of the risk that the magnet may move the metal parts of these structures.
Positron emission tomography (PET) scanning is a specialized imaging technique that uses short-lived radioactive substances to produce three-dimensional colored images of those substances functioning within the body. While CT scans and MRI scans look at anatomical structures, PET scans measure metabolic activity and functioning of tissue. PET scans can determine whether a tumor tissue is actively growing and can aid in determining the type of cells within a particular tumor.
Bone scans are used to create images of bones on a computer screen or on film. Doctors may order a bone scan to determine whether a lung cancer has metastasized to the bones. In a bone scan, a small amount of radioactive material is injected into the bloodstream and collects in the bones, especially in abnormal areas such as those involved by metastatic tumors. The radioactive material is detected by a scanner, and the image of the bones is recorded on a special film for permanent viewing.
Sputum cytology - The diagnosis of lung cancer always requires confirmation of malignant cells by a pathologist, even when symptoms and x-ray studies are suspicious for lung cancer. The simplest method to establish the diagnosis is the examination of sputum under a microscope.
If a tumor is centrally located and has invaded the airways, this procedure, known as a sputum cytology examination, may allow visualization of tumor cells for diagnosis. This is the most risk-free and inexpensive tissue diagnostic procedure, but its value is limited since tumor cells will not always be present in sputum even if a cancer is present. Also, noncancerous cells may occasionally undergo changes in reaction to inflammation or injury that makes them look like cancer cells.
Examination of the airways by bronchoscopy (visualizing the airways through a thin probe inserted in a tube through the nose or mouth) may reveal areas of tumor that can be sampled for pathologic diagnosis. A tumor in the central areas of the lung or arising from the larger airways is accessible to sampling using this technique.
Bronchoscopy may be performed using a rigid or a flexible, fiber-optic bronchoscope and can be performed in a same-day outpatient bronchoscopy suite, an operating room, or on a hospital ward. The procedure can be uncomfortable and require sedation or anesthesia. While the procedure is relatively safe
When a tumor is visualized and adequately sampled, an accurate cancer diagnosis is generally possible. Some patients may cough up dark-brown blood for one to two days after the procedure. More serious, and rare, complications include a greater amount of bleeding, decreased levels of oxygen in the blood, and heart arrythmias as well as complications from sedative medications and anesthesia.
Needle biopsy - Fine needle aspiration (FNA) through the skin, most commonly performed with radiological imaging for guidance, may be useful in retrieving cells for diagnosis from tumor nodules in the lungs. Needle biopsies are particularly useful when the lung tumor is peripherally located in the lung and not accessible to sampling by bronchoscopy.
This procedure is generally accurate when the tissue from the affected area is adequately sampled, but in some cases, adjacent or uninvolved areas of the lung may be mistakenly sampled. A small risk (3-5%) of an air leak from the lungs (called a pneumothorax, which can easily be treated) accompanies the procedure.
Major surgical procedures - If none of the aforementioned methods yields a diagnosis, surgical methods must be employed to obtain tumor tissue for diagnosis. These can include mediastinoscopy (examining the chest cavity between the lungs through a surgically-inserted probe with biopsy of tumor masses or lymph nodes)
or thoracotomy (surgical opening of the chest wall with removal of as much tumor as possible). Thoracotomy is rarely able to completely remove a lung cancer, and both mediastinoscopy and thoracotomy carry the risks of major surgical procedures (complications such as bleeding, infection, risks from anesthesia and medications).
Blood tests – While routine blood tests alone cannot diagnose lung cancer, they may reveal biochemical or metabolic abnormalities in the body that accompany cancer. For example, elevated levels of calcium or of the enzyme alkaline phosphatase may accompany cancer that is metastatic to the bones
Doctors may use several tests to accurately stage a lung cancer, including laboratory (blood chemistry) tests, x-rays, CT scans, bone scans, and MRI scans. Abnormal blood chemistry tests may signal the presence of metastases in bone or liver, and radiological procedures can document the size of a tumor as well as possible spread to other organs.
Limited stage (LS) SCLC refers to cancer that is confined to its area of origin in the chest
In extensive-stage (ES) SCLC, the cancer has spread beyond the chest to other parts of the body.
How is lung cancer treated? Treatment for lung cancer can involve surgical removal of tumor, chemotherapy, or radiation therapy, as well as combinations of these methods. The decision about which treatments will be appropriate for a given individual must take into account the localization and extent of the tumor as well as the overall health status of the patient
As with other cancers, therapy may be prescribed that is intended to be curative (removal or eradication of a cancer) or palliative (measures that are unable to cure a cancer but can reduce pain and suffering). More than one type of therapy may be prescribed. In such cases, the therapy that is added to enhance the effects of the primary therapy is referred to as adjuvant therapy. An example of adjuvant therapy is chemotherapy or radiotherapy administered after surgical removal of a tumor in order to be certain that all tumor cells are killed.
Surgery - Surgical removal of the tumor is generally performed for limited-stage (Stage I or sometimes Stage II) NSCLC and is the treatment of choice for cancer that has not spread beyond the lung. About 10-35% of lung cancers can be removed surgically, but removal does not always result in a cure, since the tumors may already have spread and can recur at a later time. Among people who have an isolated, slow-growing lung cancer removed, 25 to 40% are alive 5 years after diagnosis.
Surgery may not be possible if the cancer is too close to the trachea or if the person has other serious conditions (such as severe heart or lung disease) that would limit their ability to tolerate an operation. Surgery is less often performed with SCLC because these tumors are less likely to be localized to one area that can be removed.
The surgical procedure chosen depends upon the size and location of the tumor. Surgeons must open the chest wall and may perform a wedge resection of the lung (removal of a portion of one lobe), a lobectomy (removal of one lobe), or a pneumonectomy (removal of an entire lung). Sometimes lymph nodes in the region of the lungs are also removed (lymphadenectomy).
Surgery for lung cancer is a major surgical procedure that requires general anesthesia, hospitalization and follow-up care for weeks to months. Following the surgical procedure, patients may experience difficulty breathing, shortness of breath, pain, and weakness. The risks of surgery include complications due to bleeding, infection, and complications of general anesthesia.
Radiation - Radiation therapy may be employed as a treatment for both NSCLC and SCLC. Radiation therapy uses high-energy x-rays or other types of radiation to kill dividing cancer cells. Radiation therapy may be given as curative therapy, palliative therapy (using lower doses of radiation than with curative regimens) or as adjuvant therapy to surgery or chemotherapy.
Radiation therapy can be given if a person refuses surgery, if a tumor has spread to areas such as the lymph nodes or trachea making surgical removal impossible, or if a person has other conditions that make them too ill to undergo major surgery. Radiation therapy generally only shrinks a tumor or limits its growth when given as a sole therapy, yet in 10-15% of persons it leads to long-term remission and palliation of the cancer. Combining radiation therapy with chemotherapy can further increase the chances of survival when chemotherapy is administered.
For external radiation therapy, a process called simulation is necessary prior to treatment. Using CT scans, computers, and precise measurements, simulation maps out the exact location where the radiation will be delivered, called the treatment field or port. This process usually takes 30 minutes to two hours. The external radiation treatment itself generally is done over four or five days a week for several weeks.
Chemotherapy may be given as pills, as an intravenous infusion, or as a combination of the two. Chemotherapy treatments are usually given in an outpatient setting. A combination of drugs is given in a series of treatments, called cycles, over a period of weeks to months, with breaks in between cycles.
The side effects of chemotherapy vary according to the dosage and combination of drugs used and may also vary from individual to individual. Medications have been developed that can treat or prevent many of the side effects of chemotherapy. The side effects generally disappear during the recovery phase of the treatment or after its completion.
Treatment of recurrence – Lung cancer that has returned following treatment with surgery, chemotherapy, and/or radiation therapy is called recurrent or relapsed. If a recurrent cancer is confined to one site in the lung, it may be treated with surgery. Relapsed tumors generally do not respond to the chemotherapeutic drugs that were previously administered.
A type of chemotherapy referred to as second-line chemotherapy is used to treat recurrent cancers that have previously been treated with chemotherapy, and a number of second-line chemotherapeutic regimens have been proved effective at prolonging survival.
What is the prognosis (outcome) of lung cancer? The prognosis of lung cancer refers to the chance for recovery and is dependent upon the localization and size of the tumor, the presence of symptoms, the type of lung cancer, and the overall health status of the patient.
SCLC has the most aggressive growth of all lung cancers, with a median survival time of only 2-4 months after diagnosis when untreated. (That is, by 2-4 months, half of all patients have died.) However, SCLC is also the type of lung cancer most responsive to radiation therapy and chemotherapy.
Because SCLC spreads rapidly and is usually disseminated at the time of diagnosis, methods such as surgical removal or localized radiation therapy are less effective in treating this tumor type. However, when chemotherapy is used alone or in combination with other methods, survival time can be prolonged four- to fivefold. Of all patients with SCLC, only 5-10% are alive 5 years after diagnosis. Most of those who survive have limited stage (LS) SCLC.
In non-small cell lung cancer (NSCLC), results of standard treatment are generally poor in all but the most localized cancers that can be surgically removed. However, in Stage I cancers that can be completely removed, the 5-year survival rate can approach 75%. Radiation therapy can produce a cure in a small minority of patients with NSCLC and relief of symptoms in most patients. In advanced-stage disease, chemotherapy offers modest improvements in survival time, although overall survival rates are poor.
How can lung cancer be prevented? Smoking cessation is the most important measure that can prevent lung cancer. Many products, such as nicotine gum, nicotine sprays, or nicotine inhalers, may be helpful to people trying to quit smoking. Minimizing exposure to passive smoking is also an effective preventive measure
Using a home radon test kit can identify and allow correction of increased radon levels in the home, which can also cause lung cancers. Methods that allow early detection of cancers, such as the helical low-dose CT scan, may also be of value in the identification of small cancers that can be cured by surgical resection and prevention of widespread , incurable metastatic cancer.
Familial predisposition While the majority of lung cancers are associated with tobacco smoking, the fact that not all smokers eventually develop lung cancer suggests that other factors, such as individual genetic susceptibility, may play a role in the causation of lung cancer. Numerous studies have shown that lung cancer is more likely to occur in both smoking and non-smoking relatives of those who have had lung cancer than in the general population.
Lung diseases The presence of certain diseases of the lung, notably chronic obstructive pulmonary disease (COPD), is associated with a slightly increased risk (four to six times the risk of a nonsmoker) for the development of lung cancer even after the effects of concomitant cigarette smoking are excluded.
Air pollution Air pollution, from vehicles, industry, and power plants, can raise the likelihood of developing lung cancer in exposed individuals. Up to 1% of lung cancer deaths are attributable to breathing polluted air, and experts believe that prolonged exposure to highly polluted air can carry a risk similar to that of passive smoking for the development of lung cancer.
What are the types of lung cancer? Lung cancers, also known as bronchogenic carcinomas ("carcinoma" is another term for cancer), are broadly classified into two types: small cell lung cancers (SCLC) and non-small cell lung cancers (NSCLC). This classification is based upon the microscopic appearance of the tumor cells themselves. These two types of cancers grow and spread in different ways, so a distinction between these two types is important.
SCLC comprise about 20% of lung cancers and are the most aggressive and rapidly growing of all lung cancers. SCLC are strongly related to cigarette smoking with only 1% of these tumors occurring in non-smokers. SCLC metastasize rapidly to many sites within the body and are most often discovered after they have spread extensively. Referring to a specific cell type often seen in SCLC, these cancers are sometimes called oat cell carcinomas.
Adenocarcinomas are the most commonly seen type of NSCLC in the U.S. and comprise up to 50% of NSCLC . While adenocarcinomas are associated with smoking like other lung cancers, this type is especially observed as well in non-smokers who develop lung cancer. Most adenocarcinomas arise in the outer, or peripheral, areas of the lungs. Bronchioloalveolar carcinoma is a subtype of adenocarcinoma that frequently develops at multiple sites in the lungs and spreads along the preexisting alveolar walls.
Bronchial carcinoids account for up to 5% of lung cancers. These tumors are generally small (3-4 cm or less) when diagnosed and occur most commonly in persons under 40 years of age. Unrelated to cigarette smoking, carcinoid tumors can metastasize, and a small proportion of these tumors secrete hormone-like substances.
What is staging of lung cancer?The stage of a tumor refers to the extent to which a cancer has spread in the body. Staging involves both evaluation of a tumor’s size as well as the presence or absence of metastases in the lymph nodes or in other organs. Staging is important for determining how a particular tumor should be treated,
Lung cancer is the most common cause of cancer deaths in men and women. Prognosis depends on the extent of disease at thooe time of diagnosis. Accurate staging, assessing the extent of local and distant disease, is necessary to determine resectability and overall prognosis. Surgical resection is the only curative hope for patientswith lung cancer.
If the diagnosis is lung cancer, the doctor will want to learn the stage (or extent) of the disease. Lung cancer staging is done to find out whether the cancer has spread and, if so, to what parts of the body. Lung cancer often spreads to the brain or bones. Knowing the lung cancer stage of the disease helps the doctor plan treatment. Some tests used to determine the lung cancer stage and whether the cancer has spread include:
Radionuclide scanning. Scanning can show whether cancer has spread to other organs, such as the liver. The patient swallows or receives an injection of a mildly radioactive substance. A machine (scanner) measures and records the level of radioactivity in certain organs to reveal abnormal areas.
Bone Scan. A bone scan, one type of radionuclide scanning, can show whether cancer has spread to the bones. A small amount of radioactive substance is injected into a vein. It travels through the bloodstream and collects in areas of abnormal bone growth. An instrument called a scanner measures the radioactivity levels in these areas and records them on x-ray film.
Mediastinoscopy/Mediastinotomy. A mediastinoscopy can help show whether the cancer has spread to the lymph nodes in the chest. Using a lighted viewing instrument, called a scope, the doctor examines the center of the chest (mediastinum) and nearby lymph nodes. In mediastinoscopy, the scope is inserted through a small incision in the neck; in mediastinotomy, the incision is made in the chest. In either procedure, the scope is also used to remove a tissue sample. The patient receives a general anesthetic.
□□T1Tumor 3 cm or less in greatest dimension, surrounded by lung or visceral pleura, without bronchoscopic evidence of invasion more proximal than the lobar bronchus* (i.e., not in main bronchus)□□
T2Tumor with any of the following features or size or extent:More than 3 cm in greatest dimension Involves main bronchus, 2 cm or more distal to the carina Invades the visceral pleura Associated with atelectasis or obstructive pneumonitis that extends toThe hilar region but does not involve the entire lung□□
directly invades any of the following: chest wall (including superior sulcus tumors), diaphragm, mediastinal pleura, parietal pericardium; or tumor in the main bronchus less than 2 cm distal to the carina but or without involvement of the carina; or associated atelectasis obstructive pneumonitis of the entire lung
T4Tumor of any size that invades any of the following: mediastinum, heart,great vessels, trachea, esophagus,vertebral body, carina; separate tumor nodule(s) in the same lobe; or tumor with a malignant pleural effusion*** The uncommon superficial tumor of any size with its invasive component
Stage IIIA Lung Cancer. The cancer has spread from the lung to lymph nodes beyond the lung area. Cancer usually isn't treated surgically at this stage. There is a 15 percent to 30 percent chance of surviving 5 years when the disease is caught and treated with radiation or chemotherapy at this point.
The role of invasive staging and the specific procedures utilized deserve mention. Distinction must be made between clinical stage and pathological stage. The former is based solely on non –invasive imaging, where as the latter depends on actual histologic material obtaine deither by invasive staging or at the time of the surgical resection.
Moreover, scientists have used these clonal genetic alterations to detect rare neoplastic cells in surgical margins of HNSCC patients and in the sputum of patients with lung cancer. This HNSCC model will now serve as a template to identify and characterize critical regions of chromosomal loss in non-small cell lung cancer and the development of a comprehensive molecular progression model for lung cancer
They have already confirmed that critical genetic events in HNSCC, such as loss at chromosome 9p21 also occur in lung cancer and these will now be characterized for their occurrence and timing in lung cancer progression. Moreover, tumor suppressor genes from two important regions of loss will be evaluated for inactivation in primary lung cancers
Early genetic events in lung cancer progression will be used to further develop novel diagnostic and staging strategies in the clinical setting. These novel approaches demonstrate the value of developing genetic progression models to augment translational projects based on emerging molecular knowledge.
In addition, it is determined that incremental increases in DNA methyltransferase activity (DNA-MTase), which is the enzyme responsible for catalyzing DNA methylation, accompany progression steps in lung and other tumor types. They will test the utility of visualizing the cell populations responsible for this change for providing new means to clinically assess the earliest stages of, and risk status for, lung cancer.